The dominant source of variance between biopsies from the same tumour was due to intratumoural heterogeneity, Dr Lau's group found. However, the extent of that variation depended on the particular gene or groups of genes being studied.
"Some genes, such as ESR1 and HER2, are very consistently expressed across the tissue, thus gene expression measurements display little variation between biopsies. However, other genes such as MKI67, which is known to be highly variable, is expressed less consistently, and therefore can produce vastly different results depending on the area of the tumour that is sampled," Dr Lau says.
For the first time, Dr Lau's group also showed how combining samples of two or three biopsies from a single breast tumour could effectively overcome this variation for selected genes.
"Differences between tumours are much greater than variability within a tumour or a test. Our current study shows that we can get a comprehensive picture of the genes being expressed in the tumour by sampling multiple areas of the tumour and pooling the samples together. This increases the precision of the assay and allows us to make more reliable predictions related to the disease. The trade-off is that intratumoural heterogeneity is also averaged to a single, more consistent measurement."
This study is an excellent example of how researchers are rising to the challenges of tumour heterogeneity, comments Prof Charles Swanton, Chair in Personalised Cancer Medicine at the UCL Cancer Institute in London and from the Cancer Research UK London Research Institute, member of the ESMO Translational Research Working Group, who was not involved in the study.
"Developing accurate biomarkers that are not subject to real tumour sampling bi
|Contact: Vanessa Pavinato|
European Society for Medical Oncology